An auto-photoacoustic melanin-based drug delivery nano-platform for self-monitoring of acute kidney injury therapy via a triple-collaborative strategy

活性氧 氧化应激 药物输送 细胞凋亡 体内分布 材料科学 体内 聚ADP核糖聚合酶 急性肾损伤 药理学 纳米技术 化学 医学 生物化学 体外 生物 聚合酶 生物技术 内科学 基因
作者
Xuhui Zhao,Jinghua Sun,Jie Dong,Chunyan Guo,Wenwen Cai,Juanjuan Han,Hao Shen,Shuxin Lv,Ruiping Zhang
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:147: 327-341 被引量:25
标识
DOI:10.1016/j.actbio.2022.05.034
摘要

Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to toxic reactive oxygen species (ROS), apoptosis, and inflammation. Excessive activation of poly (ADP-ribose) polymerase-l (PARP-1) by ROS can cause mitochondrial dysfunction and release of the proapoptotic protein AIF, which triggers an intrinsic PARP-1-dependent cell death program. Considering these characteristics of rhabdomyolysis-induced AKI, we developed a targeting nanodrug delivery platform by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) that could realize photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory). The nanoparticles exhibited good dispersibility, solubility, and broad-spectrum ROS scavenging ability. In vitro experiments revealed high biocompatibility of the GMP nanoparticles and strong ability of scavenging multiple toxic ROS, antiapoptotic activity, and anti-inflammatory activity. Because melanin nanoparticles possess inherent photoacoustic (PA) imaging capability, they can not only serve as a drug carrier but also perform self-monitoring for real-time tracking of GMP biodistribution and renal uptake in a murine AKI model through PA imaging. In vivo experiments showed that the GMP nanoparticles could effectively reduce oxidative stress, apoptosis, and inflammatory response in mice with rhabdomyolysis-induced AKI, and the mechanism of alleviation was verified through western blot experiments. These results indicated that the nanoplatform could realize the targeted delivery and curative effect monitoring under the guidance of PA imaging, which is of great significance for the prevention and treatment of AKI. A targeting nanodrug delivery platform was developed by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) for photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory) of acute kidney injury (AKI). Further studies indicated that the Keap-1/Nrf2/HO-1 and PARP-1/AIF signaling pathways are involved in the therapeutic mechanisms to alleviate AKI. Immunohistochemical staining and routine blood test confirmed the anti-inflammatory performance of GMP nanoparticles. Compared to exogenous nanomaterials, we used endogenous melanin with broad ROS scavenging capacity as the nanocarrier and antioxidant, which not only overcomes the defects of high specificity, potential toxicity, low loading capacity, and high cost but also shows good biosafety and photoacoustic imaging performance in vivo.
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